The UCLA Transgenic Mouse/ES Cell Shared Resource provides a multi-faceted operation for producing targeted genetic alterations in embryonic stem (ES) cells, generating transgenic and gene-targeted (chimeric) mice, and re-derivation of genetically engineered strains to obtain pathogen-free mice. The Shared Resource strives to provide these services in a cost-effective manner, with the highest scientific and quality standards. The UCLA Transgenic Mouse/ES Cell Shared Resource performs: 1) ES cell electroporation, selection and propagation of correctly targeted clones; 2) injection of these clones into blastocysts to produce chimeric mice; and 3) pronuclear injections of engineered DNA constructs to produce transgenic animals. In addition, the Shared Resource carries out re-derivation and recovery of genetically modified mouse strains. The Shared Resource provides select reagents, such as quality-assured ES cells and feeder cell lines, as well as general DNA vectors, to investigators wishing to initiate transgenic/gene-targeting projects. The professional and technical staff are experienced and knowledgeable in all areas of the work, and assist investigators in the design and assembly of DNA constructs, in the options available in transgenic and gene targeting experiments to yield the desired animal, in providing advice on animal husbandry and breeding, and in evaluating and implementing new techniques that better serve the Shared Resources? clients. The Shared Resource has enhanced the ability of Cancer Center members to pursue cancer research at UCLA, particularly for investigators beginning transgenic/gene knockout projects. The ability to pursue cancer investigations in an intact animal is a goal that the Shared Resource can help investigators to achieve. The Shared Resource is in a key position to assist investigators in discovering/verifying the function of unknown/known genes, and in transferring the genomic sequences obtained from both the human and the mouse into animal models of human diseases.